Brain Metabolism but Not Gray Matter Volume Underlies the Presence of Language Function in the Minimally Conscious State (MCS): MCS+ Versus MCS− Neuroimaging Differences

Abstract

Background. The minimally conscious state (MCS) is subcategorized into MCS− and MCS+, depending on the absence or presence, respectively, of high-level behavioral responses such as command-following. Objective. We aim to investigate the functional and structural neuroanatomy underlying the presence of these responses in MCS− and MCS+ patients. Methods. In this cross-sectional retrospective study, chronic MCS patients were diagnosed using repeated Coma Recovery Scale–Revised assessments. Fluorodeoxyglucose-positron emission tomography data were acquired on 57 patients (16 MCS−; 41 MCS+) and magnetic resonance imaging with voxel-based morphometry analysis was performed on 66 patients (17 MCS−; 49 MCS+). Brain glucose metabolism and gray matter integrity were compared between patient groups and control groups. A metabolic functional connectivity analysis testing the hypothesis of preserved language network in MCS+ compared with MCS− was also done. Results. Patients in MCS+ presented higher metabolism mainly in the left middle temporal cortex, known to be important for semantic processing, compared with the MCS− group. The left angular gyrus was also functionally disconnected from the left prefrontal cortex in MCS− compared with MCS+ group. No significant differences were found in gray matter volume between patient groups. Conclusions. The clinical subcategorization of MCS is supported by differences in brain metabolism but not in gray matter structure, suggesting that brain function in the language network is the main support for recovery of command-following, intelligible verbalization and/or intentional communication in the MCS. Better characterizing the neural correlates of residual cognitive abilities of MCS patients contributes to reduce their misdiagnosis and to adapt therapeutic approaches.

Covert Cognition in Disorders of Consciousness: A Meta-Analysis

“…This is not surprising, as, by definition, on the contrary to MCS+, patients in a MCS− are unable to show that they understand language (e.g., behavioral response to command). In the literature, the clinical subcategorization of MCS is further supported by metabolic differences in areas that are associated with consciousness (i.e., lower metabolism in precuneus and thalamus in MCS−) [41] and with both receptive and expressive language (i.e., lower metabolism in the left middle temporal cortex and lower connectivity between left angular gyrus and left prefrontal cortex in MCS−) [42,43]. The detection of covert cognition in MCS− suggests that, in a fraction of these patients, receptive language impairment might not be the limiting factor when assessing consciousness at the bedside but expressive language impairments (and hence motor limitations) might be.…”

Language Assessment in Patients with Disorders of Consciousness

“…Using fluorodeoxyglucose (FDG)-PET, higher brain glucose metabolism was observed in left-side language-related cortical areas in MCS+ patients compared to MCS − patients. 63 64 65 Stronger brain connectivity in a left frontoparietal network was also observed using both resting state fMRI and FDG-PET in MCS+ compared to MCS − . 63 64 66 A recent study also supports the association between the level of preservation of the language network and the CRS-R auditory subscale scores (including the command-following item).…”

“…63 64 65 Stronger brain connectivity in a left frontoparietal network was also observed using both resting state fMRI and FDG-PET in MCS+ compared to MCS − . 63 64 66 A recent study also supports the association between the level of preservation of the language network and the CRS-R auditory subscale scores (including the command-following item). 67 By examining white matter integrity, Zheng et al 68 showed an increased structural connectivity for thalamo-premotor and thalamo-temporal pathways in MCS+ compared to MCS− patients.…”

“…No significant grey matter volume, in language-related or other cortical areas, could, however, distinguish MCSÀ from MCSþ groups. 64,69 Studies using EEG methodology to distinguish DoC patients able to respond to commands from those who are not 70 observed an increase in central gamma and posterior (centro-occipital) alpha power as well as in complexity measures such as alpha permutation entropy (i.e., assessing the dynamics of a time series). A few studies focused more directly on language-related behavior, beyond the simple MCSþ versus MCSÀ distinction.…”

Effectiveness of transcranial direct current stimulation over dorsolateral prefrontal cortex in patients with prolonged disorders of consciousness: A systematic review and meta-analysis

“…PDOC can be divided into unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) according to the degree of retention of awareness ( 6 ). UWS is also traditionally called as vegetative state (VS), and MCS can be further divided into MCS- and MCS+ ( 7 , 8 ). We can use the Coma Recovery Scale Revised (CRS-R) to infer the degree of consciousness retention through the behavioral characteristics of patients and make differential diagnosis for PDOC ( 9 , 10 ).…”